Climate warming is expected to reduce oxygen (O-2) supply to the ocean and expand its oxygen minimum zones (OMZs). We reconstructed variations in the extent of North Pacific anoxia since 1850 using a geochemical proxy for denitrification (delta N-15) from multiple sediment cores. Increasing delta N-15 since similar to 1990 records an expansion of anoxia, consistent with observed O-2 trends. However, this was preceded by a longer declining delta N-15 trend that implies that the anoxic zone was shrinking for most of the 20th century. Both periods can be explained by changes in winds over the tropical Pacific that drive upwelling, biological productivity, and O-2 demand within the OMZ. If equatorial Pacific winds resume their predicted weakening trend, the ocean's largest anoxic zone will contract despite a global O-2 decline.